Why is HIV Fatal.docx

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School

University of Guelph

Department

Statistics

Course

STAT 2230

Professor

Dan Meegan

Semester

Fall

Description

Why is HIV Fatal?
 The idea that evolution by natural selection, is an automatic process that simply happens whenever a
population shows the necessary heritable variation in survival and reproductive success
o Traits conducive to surviving and reproducing spread throughout the population; traits conducive
to dying without issue disappear
Short-Sighted Evolution
 If there is a resistant to HIV and Aids, then we can expect that resistance will spread throughout the
human population as generations pass
 Antibodies and killer T cells recognize HIV and HIV-infected cells by binding to epitopes- short pieces of
viral protein displayed on the surface of the virion or the infected cell
o These epitopes are encoded in HIV’s genes
 Mutations in the genes can change the epitopes and may enable the mutant virion to evade detection by
the host’s current arsenal of antibodies and killer T cells
 As the infection progresses from the acute phase to the chronic phase, the HIV population has already
evolved
 Variants easily recognized by the first wave of the immune attack have disappeared; variants less easily
recognized persist
 Because the immune system never completely curtails HIV’s replication, the HIV population inside a host
evolves throughout the chronic phase of infection
 The evolution of the HIV population appears to contribute to the collapse of the immune system in at
least three ways
o First- it is the continuous evolution toward novel epitopes that enables the viral population to
stay far enough ahead of the immune response to keep replicating in high numbers---these novel
epitopes will enable the viral population to be undetected by the immune cells of the host’s body
 Eventually, the continuously replicating viral population burns through the host’s supply
of naive and memory T cells and destroys the body’s ability to replace them
o Second- the viral population within most hosts evolves toward ever more aggressive replication
 The longer a patient harbours an HIV population, the more damaging the virions in the
population become
o Third- in at least half of all hosts- and possibly many more- strains of HIV evolve that can infect
naive T cells
 An HIV virion’s ability to infect a given cell type is determined by the coreceptor the
virion uses
 The coreceptor is the second of two proteins the HIV latches onto to infiltrate a
host cell
 Early in most HIV infections, most virions in the HIV population use as their
coreceptor a protein called CCR5
o CCR5 is found on dendritic cells, macrophages, and regulatory, resting,
and effector T cells
 As the infection progresses and the HIV populations evolves, virions often
emerge that exploit a different coreceptor, a protein called CXCR4
 CXCR4 is found on naive T cells
 Because naive T cells are the progenitors of memory and effector T cells, the emergence of virions that
can infect and kill naive T cells is typically bad news for the host
 The rapid evolution of the HIV population inside a host hastens the collapse of the host’s immune system.
This evolution is short-sighted because it also hastens the extinction of the HIV population.
 The evolution of the HIV population within a host is short-sighted
 The virions do not look to the future and anticipate that as their population evolves it will ultimately kill its
host and thereby cause its own extinction
 The virions cant look to the future, they are just tiny, thoughtless molecular machines
 Evolution by natural selection does not look to the future either o It can’t; it is just a mathematical process that happens automatically
 Therefore, the HIV population in any particular host ultimately evolves itself right out of
existence
 HIV infection is fatal, because of the short-sighted evolution of the HIV population inside the host
o Lethal strains of HIV become predominant in the host because they enjoy a short-term
advantage in survival and reproduction
A Correlation between Lethality and Transmission?
 Sh